dc.contributor.author | Maas, Roeltje R | |
dc.contributor.author | Soukup, Klara | |
dc.contributor.author | Fournier, Nadine | |
dc.contributor.author | Massara, Matteo | |
dc.contributor.author | Galland, Sabine | |
dc.contributor.author | Kornete, Mara | |
dc.contributor.author | Wischnewski, Vladimir | |
dc.contributor.author | Lourenco, Joao | |
dc.contributor.author | Croci, Davide | |
dc.contributor.author | Álvarez-Prado, Ángel F | |
dc.contributor.author | Marie, Damien N | |
dc.contributor.author | Lilja, Johanna | |
dc.contributor.author | Marcone, Rachel | |
dc.contributor.author | Calvo, Gabriel F | |
dc.contributor.author | Santalla Mendez, Rui | |
dc.contributor.author | Aubel, Pauline | |
dc.contributor.author | Bejarano, Leire | |
dc.contributor.author | Wirapati, Pratyaksha | |
dc.contributor.author | Ballesteros, Iván | |
dc.contributor.author | Hidalgo, Andrés | |
dc.contributor.author | Hottinger, Andreas F | |
dc.contributor.author | Brouland, Jean-Philippe | |
dc.contributor.author | Daniel, Roy T | |
dc.contributor.author | Hegi, Monika E | |
dc.contributor.author | Joyce, Johanna A | |
dc.date.accessioned | 2024-05-09T13:45:16Z | |
dc.date.available | 2024-05-09T13:45:16Z | |
dc.date.issued | 2023-10-12 | |
dc.identifier.citation | Cell. 2023 Oct 12;186(21):4546-4566.e27. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19334 | |
dc.description.abstract | Neutrophils are abundant immune cells in the circulation and frequently infiltrate tumors in substantial numbers. However, their precise functions in different cancer types remain incompletely understood, including in the brain microenvironment. We therefore investigated neutrophils in tumor tissue of glioma and brain metastasis patients, with matched peripheral blood, and herein describe the first in-depth analysis of neutrophil phenotypes and functions in these tissues. Orthogonal profiling strategies in humans and mice revealed that brain tumor-associated neutrophils (TANs) differ significantly from blood neutrophils and have a prolonged lifespan and immune-suppressive and pro-angiogenic capacity. TANs exhibit a distinct inflammatory signature, driven by a combination of soluble inflammatory mediators including tumor necrosis factor alpha (TNF-ɑ) and Ceruloplasmin, which is more pronounced in TANs from brain metastasis versus glioma. Myeloid cells, including tumor-associated macrophages, emerge at the core of this network of pro-inflammatory mediators, supporting the concept of a critical myeloid niche regulating overall immune suppression in human brain tumors. | es_ES |
dc.description.sponsorship | We thank the Departments of Neurosurgery, Neuro-oncology, and Pathology at
CHUV Lausanne; Dr. Florian Klemm; members of Prof. Hegi’s lab; and Prof. Ron
Stoop for generous collaboration in obtaining and processing patient samples.
We thank Dr. Benoit Duc for helping collect HD blood and Dr. Spencer Watson
and Paola Guerrero for insightful advice on QuPath image quantification. We
gratefully acknowledge all current and former members of Prof. Joyce’s lab,
and members of the laboratories of Profs. Tacchini-Cottier, Meylan, De Palma,
Petrova and Pittet, for insightful discussions and advice. We thank V. Noguet
Brechbu¨ hl (Mouse Pathology Facility) for expert preparation of tissue sections;
all members of the Epalinges and Agora animal facilities; P. Baumgartner and
A.-C. Thierry for advice and technical support on multiplex cytokine arrays;
and all members of the UNIL Flow Cytometry Facility for expert guidance in
designing panels and performing FAC-sorting. We used Biorender to prepare
the graphical abstract and several figure infographics. This research was supported by theBreast Cancer Research Foundation, Carigest Foundation, Fondation ISREC, Ludwig Institute for Cancer Research, Swiss Bridge Award, Swiss
National Science Foundation Advanced Grant TMAG-3_209224, and University
of Lausanne (to J.A.J.). K.S. was funded by an Erwin-Schro¨ dinger Fellowship
from the Austrian Science Fund (FWF, J4343-B28); M.M. received funding
from AIRC and European Union’s Horizon 2020 research and innovation
programme under the Marie Sk1odowska Curie (grant agreement 800924);
S.G. was supported by Fondation Leenaards and Fondation ISREC;
A.F.A.-P. was supported by an EMBO Long-Term Postdoctoral Fellowship
(EMBO ALTF 654-2019) and a Marie Sk1odowska Curie Actions Individual
Fellowship (MSCA-IF 890933); G.F.C. is supported by MCIN/AEI/10.13039/501
100011033 (grant PID2019-110895RB-I00) and by Junta de Comunidades de
Castilla-La Mancha (SBPLY/19/180501/000211); R.S.M. is supported by the European Union’s Horizon 2020 research and innovation program under the Sk1odowska Curie grant agreement (grant agreement 955951, Evomet ITN); L.B. was
supported by the European Molecular Biology Organisation (ALTF 1193-2018)
and the Human Frontier Science Program (LT000038/2019); A.H. is funded by
FET-OPEN (no. 861878) from the European Commission. The CNIC is supported
by the MCIN and the Pro CNIC Foundation and is a Severo Ochoa Center of
Excellence (CEX2020-001041-S). Our particular gratitude is extended to all patients and healthy volunteers who generously donated tissue for analyses, and
without whom this study would not have been possible. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Cell Press | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.title | The local microenvironment drives activation of neutrophils in human brain tumors. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 37769657 | es_ES |
dc.format.volume | 186 | es_ES |
dc.format.number | 21 | es_ES |
dc.format.page | 4546 | es_ES |
dc.identifier.doi | 10.1016/j.cell.2023.08.043 | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1097-4172 | es_ES |
dc.relation.publisherversion | 10.1016/j.cell.2023.08.043 | es_ES |
dc.identifier.journal | Cell | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Imagen de la Inflamación Cardiovascular y la Respuesta Inmune | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |